Telange Darshan R, Bhaktani Neha M, Hemke Atul T, Pethe Anil M, Agrawal Surendra S, Rarokar Nilesh R, Jain Shirish P
Datta Meghe College of Pharmacy, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Sawangi (Meghe), Wardha 442002, Maharashtra, India.
Smt. Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India.
ACS Omega. 2023 Jul 5;8(28):25195-25208. doi: 10.1021/acsomega.3c02280. eCollection 2023 Jul 18.
Atorvastatin (ATV), a lipid-lowering agent, has low oral bioavailability due to its poor water solubility, permeability, and low dissolution rate. Therefore, pentaerythritol-EudragitRS100 co-processed excipients (PECE) were synthesized, and their feasibility as solid dispersion carriers (ATV-PECE-SD) for improving the solubility, permeability, and dissolution rate of ATV was explored. Solid dispersions were assessed in terms of particle size and zeta potential, and solubility, dissolution, and permeation studies were studied. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) were used as characterization tools. ATV-PECE-SD3 (1:4) formulations exhibited a small particle size with high stability. Physicochemical evaluation evidenced the formation of solid dispersion due to the involvement of weak electrostatic interaction between the polar functional groups of ATV and PECE carriers. ATV-PECE-SD3 (1:4) significantly enhanced the water solubility by ∼43-fold compared to pure ATV. dissolution studies showed that optimized formulation enhanced the dissolution rate of ATV compared to pure ATV. permeation results revealed that ATV-PECE-SD3 (1:4) enhanced the permeation rate of ATV compared to pure ATV. The optimized formulations significantly improved the dissolution rate of ATV in the fed state due to the food effect and micelle formation mechanism compared to the fasted state. The study concludes that co-processed excipients could be used as promising solid dispersion carriers to enhance the aqueous solubility, permeability, and dissolution rate of ATV.
阿托伐他汀（ATV）是一种降脂药物，由于其水溶性差、渗透性低和溶解速率慢，口服生物利用度较低。因此，合成了季戊四醇-丙烯酸树脂RS100共处理辅料（PECE），并探讨了其作为固体分散体载体（ATV-PECE-SD）提高ATV溶解度、渗透性和溶解速率的可行性。对固体分散体进行了粒径和zeta电位评估，并进行了溶解度、溶出度和渗透研究。使用扫描电子显微镜（SEM）、傅里叶变换红外光谱（FT-IR）、差示扫描量热法（DSC）和粉末X射线衍射（PXRD）作为表征工具。ATV-PECE-SD3（1:4）制剂呈现出粒径小且稳定性高的特点。物理化学评估证明，由于ATV的极性官能团与PECE载体之间存在弱静电相互作用，从而形成了固体分散体。与纯ATV相比，ATV-PECE-SD3（1:4）显著提高了约43倍的水溶性。溶出度研究表明，与纯ATV相比，优化后的制剂提高了ATV的溶出速率。渗透结果显示，与纯ATV相比，ATV-PECE-SD3（1:4）提高了ATV的渗透速率。与禁食状态相比，由于食物效应和胶束形成机制，优化后的制剂在进食状态下显著提高了ATV的溶出速率。该研究得出结论，共处理辅料可作为有前景的固体分散体载体，以提高ATV的水溶性、渗透性和溶解速率。
